Antibiotic Restistance

The Antibiotic Arsenal

Introduction | Antibiotics in Human Medicine | The Antibiotic Arsenal | Antimicrobial Use in Food Animals | Solutions to the Resistance Problem

Image of many types of pills, antibiotics, and more

Since the first antibiotics were discovered and developed in the late 1920s, we’ve developed an impressive arsenal against disease-causing microbes. We have more than 100 individual antibiotic weapons.

Many of these are chemical cousins of one another — variations of the original infection-fighting agents found in nature that have been tweaked chemically to make them more potent or less likely to cause side effects. Related antibiotics are lumped together in groups called classes based on their chemical structure.

All but one were developed more than 40 years ago.

The new millennium brought an important new class of antibiotics: the Oxazolidinones. This class so far contains only one drug, linezolid (sold under the brand name Zyvox™).

Linezolid was formally approved for use by the Food and Drug Administration on April 17, 2000. It inhibits bacterial protein production and is active against gram-positive bacteria, including stubborn strains of Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecium that have become resistant to the other antibiotics historically used against them.

Courtesy of Sylvester McKenna & Devabrata Mondal, Long Island University, Brooklyn Campus.

The approval of linezolid took some of the edge off the growing anxiety caused by the increasing emergence of potentially deadly bacteria resistant to drugs formerly used to treat them, including a particularly potent antibiotic called vancomycin that is often used as the treatment of last resort.

	HOW MICROBES FIGHT OFF DRUGS
	Change the locks Many drugs work by binding to specific target molecules on microbial cell surfaces, like a key fitting into a lock. Over time, microbes adapt by altering the shape of their surface molecules, changing the locks, so to speak, to keep the intruding drug out. Build drug “sump pumps” For many antibiotics to work, they have to get inside the germ’s cell. Clever bacteria, faced with poisons flowing into their cells, developed molecular efflux pumps that act like miniature sump pumps. As fast as the drug flows in, the efflux pumps channel it right back out again. Build intercept-and-destroy weapons Human armies use anti-tank and anti-aircraft missiles; microbial forces deploy anti-drug enzymes. For example, bacteria can inactivate penicillin by producing an enzyme called beta-lactamase that breaks apart key chemical bonds in the drug. Bypass critical functions When drugs inactivate or destroy critical proteins, some microbes adapt by developing alternate proteins or steps to continue functioning. For example, the drug methicillin targets a key protein in bacteria. Drug-resistant Staphylococcus aureus bacteria produce a second protein that performs the same function as the protein methicillin targets, only this alternate protein is different enough that methicillin doesn’t recognize it and so can’t latch onto and inhibit it.

Because linezolid can inactivate even these drug-resistant bugs, many experts are urging that it be used judiciously and not be dispensed at the drop of a prescription pad. Their thinking is that even a new antibiotic with a whole new way of thwarting bacteria will eventually lose its potency as bacteria inevitably develop resistance to it sometime down the line. Limiting linezolid’s use could help in postponing that event.

A year after linezolid’s approval, a researcher reported in the April 13, 2001, issue of the medical journal Lancet that three patients with vancomycin-resistant Enterococcus faecium developed resistance to the new drug after a long period of treatment.

We’re in an arms race with pathogenic microbes. Even as we develop new weapons, they adapt new defenses. That’s why discovery and development of new antimicrobial agents are such important endeavors.

A survey by the Pharmaceutical Research and Manufacturers of America found that 137 new medicines to treat infectious disease were undergoing clinical testing or awaiting government approval in 2000. Of these, 19 were new antibiotics designed to overcome antibiotic resistance. As encouraging as that may be, only one of five drugs tested in clinical trials is approved for use in humans.

Introduction | Antibiotics in Human Medicine | The Antibiotic Arsenal | Antimicrobial Use in Food Animals | Solutions to the Resistance Problem